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https://www.readbyqxmd.com/read/27926940/inflammasome-independent-nlrp3-restriction-of-a-protective-early-neutrophil-response-to-pulmonary-tularemia
#1
Sivakumar Periasamy, Hongnga T Le, Ellen B Duffy, Heather Chin, Jonathan A Harton
Francisella tularensis (Ft) causes a frequently fatal, acute necrotic pneumonia in humans and animals. Following lethal Ft infection in mice, infiltration of the lungs by predominantly immature myeloid cells and subsequent myeloid cell death drive pathogenesis and host mortality. However, following sub-lethal Ft challenge, more mature myeloid cells are elicited and are protective. In addition, inflammasome-dependent IL-1β and IL-18 are important for protection. As Nlrp3 appears dispensable for resistance to infection with Francisella novicida, we considered its role during infection with the virulent Type A strain SchuS4 and the attenuated Type B live vaccine strain LVS...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27918958/drivers-of-airborne-human-to-human-pathogen-transmission
#2
REVIEW
Sander Herfst, Michael Böhringer, Basel Karo, Philip Lawrence, Nicola S Lewis, Michael J Mina, Charles J Russell, John Steel, Rik L de Swart, Christian Menge
Airborne pathogens - either transmitted via aerosol or droplets - include a wide variety of highly infectious and dangerous microbes such as variola virus, measles virus, influenza A viruses, Mycobacterium tuberculosis, Streptococcus pneumoniae, and Bordetella pertussis. Emerging zoonotic pathogens, for example, MERS coronavirus, avian influenza viruses, Coxiella, and Francisella, would have pandemic potential were they to acquire efficient human-to-human transmissibility. Here, we synthesize insights from microbiological, medical, social, and economic sciences to provide known mechanisms of aerosolized transmissibility and identify knowledge gaps that limit emergency preparedness plans...
December 2, 2016: Current Opinion in Virology
https://www.readbyqxmd.com/read/27905529/efficient-targeted-mutagenesis-of-rice-and-tobacco-genomes-using-cpf1-from-francisella-novicida
#3
Akira Endo, Mikami Masafumi, Hidetaka Kaya, Seiichi Toki
CRISPR/Cas9 systems are nowadays applied extensively to effect genome editing in various organisms including plants. CRISPR from Prevotella and Francisella 1 (Cpf1) is a newly characterized RNA-guided endonuclease that has two distinct features as compared to Cas9. First, Cpf1 utilizes a thymidine-rich protospacer adjacent motif (PAM) while Cas9 prefers a guanidine-rich PAM. Cpf1 could be used as a sequence-specific nuclease to target AT-rich regions of a genome that Cas9 had difficulty accessing. Second, Cpf1 generates DNA ends with a 5' overhang, whereas Cas9 creates blunt DNA ends after cleavage...
December 1, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881415/whole-genome-relationships-among-francisella-bacteria-of-diverse-origin-define-new-species-and-provide-specific-regions-for-detection
#4
Jean F Challacombe, Jeannine M Petersen, La Verne Gallegos-Graves, David Hodge, Segaran Pillai, Cheryl R Kuske
Francisella tularensis (Ft) is a highly virulent zoonotic pathogen that causes tularemia, and because of weaponization efforts in past world wars, is considered a Tier 1 biothreat agent. Detection and surveillance of Ft may be confounded by the presence of uncharacterized, closely related organisms. Through DNA-based diagnostics and environmental surveys, novel clinical and environmental Francisella isolates have been obtained in recent years. Here we present 17 new Francisella genomes and a comparison of their characteristics to each other and to 14 publicly available genomes as well as a comparative analysis of 16S rRNA and sdhA genes from over 90 Francisella strains...
November 23, 2016: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/27854567/metagenomic-evaluation-of-bacteria-from-voles
#5
Katja A Koskela, Laura Kalin-Mänttäri, Heidi Hemmilä, Teemu Smura, Paula M Kinnunen, Jukka Niemimaa, Heikki Henttonen, Simo Nikkari
Voles (Arvicolinae, Rodentia) are known carriers of zoonotic bacteria such as Bartonella spp. and Francisella tularensis. However, apart from F. tularensis, the bacterial microbiome of voles has not previously been determined in Finland and rarely elsewhere. Therefore, we studied liver samples from 61 voles using 16S ribosomal RNA gene PCR analysis, followed by Sanger sequencing. Twenty-three of these samples were also studied with tag-encoded pyrosequencing. The samples originated from 21 field voles (Microtus agrestis), 37 tundra voles (Microtus oeconomus), and 3 bank voles (Myodes glareolus)...
November 17, 2016: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/27847371/sensitive-detection-of-francisella-tularensis-directly-from-whole-blood-using-the-genexpert-system
#6
Padmapriya P Banada, Srinidhi Deshpande, Soumitesh Chakravorty, Riccardo Russo, James Occi, Gabriel Meister, Kelly J Jones, Carl H Gelhaus, Michelle W Valderas, Martin Jones, Nancy Connell, David Alland
BACKGROUND: Francisella tularensis is a potential bioterrorism agent that is highly infectious at very low doses. Diagnosis of tularemia by blood culture and nucleic acid based diagnostic tests are insufficiently sensitive. Here, we demonstrate a highly sensitive, F. tularensis assay that incorporates sample processing and detection into a single cartridge suitable for point of care detection. METHODS: Assay limit of detection (LOD) and dynamic range were determined in a filter based cartridge run on the GeneXpert system...
November 9, 2016: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/27842441/identification-of-two-substrates-of-fts_1067-protein-an-essential-virulence-factor-of-francisella-tularensis
#7
Petra Spidlova, Iva Senitkova, Marek Link, Jiri Stulik
Francisella tularensis is a highly virulent intracellular pathogen with the capacity to infect a variety of hosts including humans. One of the most important proteins involved in F. tularensis virulence and pathogenesis is the protein DsbA. This protein is annotated as a lipoprotein with disulfide oxidoreductase/isomerase activity. Therefore, its interactions with different substrates, including probable virulence factors, to assist in their proper folding are anticipated. We aimed to use the immunopurification approach to find DsbA (gene locus FTS_1067) interacting partners in F...
November 15, 2016: Acta Microbiologica et Immunologica Hungarica
https://www.readbyqxmd.com/read/27832588/secreted-effectors-encoded-within-and-outside-of-the-francisella-pathogenicity-island-promote-intramacrophage-growth
#8
Aria Eshraghi, Jungyun Kim, Alexandra C Walls, Hannah E Ledvina, Cheryl N Miller, Kathryn M Ramsey, John C Whitney, Matthew C Radey, S Brook Peterson, Brittany R Ruhland, Bao Q Tran, Young Ah Goo, David R Goodlett, Simon L Dove, Jean Celli, David Veesler, Joseph D Mougous
The intracellular bacterial pathogen Francisella tularensis causes tularemia, a zoonosis that can be fatal. The type VI secretion system (T6SS) encoded by the Francisella pathogenicity island (FPI) is critical for the virulence of this organism. Existing studies suggest that the complete repertoire of T6SS effectors delivered to host cells is encoded by the FPI. Using a proteome-wide approach, we discovered that the FPI-encoded T6SS exports at least three effectors encoded outside of the island. These proteins share features with virulence determinants of other pathogens, and we provide evidence that they can contribute to intramacrophage growth...
November 9, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27830989/a-mutagenesis-based-approach-identifies-amino-acids-in-the-n-terminal-part-of-francisella-tularensis-igle-that-critically-control-type-vi-system-mediated-secretion
#9
Jeanette E Bröms, Lena Meyer, Anders Sjöstedt
The Gram-negative bacterium Francisella tularensis is the etiological agent of the zoonotic disease tularemia. Its life cycle is characterized by an ability to survive within phagocytic cells through phagosomal escape and replication in the cytosol, ultimately causing inflammasome activation and host cell death. Required for these processes is the Francisella pathogenicity island (FPI), which encodes a Type VI secretion system (T6SS) that is active during intracellular infection. In this study, we analyzed the role of the FPI-component IglE, a lipoprotein which we previously have shown to be secreted in a T6SS-dependent manner...
November 10, 2016: Virulence
https://www.readbyqxmd.com/read/27828762/seroprevalence-of-borrelia-burgdorferi-anaplasma-phagocytophilum-and-francisella-tularensis-infections-in-belgium-results-of-three-population-based-samples
#10
Mathilde De Keukeleire, Sophie O Vanwambeke, Christel Cochez, Paul Heyman, David Fretin, Véronique Deneys, Victor Luyasu, Benoît Kabamba, Annie Robert
To estimate the seroprevalence of Borrelia burgdorferi (Bb), Anaplasma phagocytophilum (Ap), and Francisella tularensis (Ft) in Belgium, we tested sera from three population-based samples in which exposure to pathogen is assumed to vary: 148 samples from workers professionally exposed, 209 samples from rural blood donors, and 193 samples from urban blood donors. Sera were tested using ELISA or the immunofluorescence assay test. The seroprevalence of Bb was 5.4% in workers professionally exposed, 2.9% in rural blood donors, and 2...
November 9, 2016: Vector Borne and Zoonotic Diseases
https://www.readbyqxmd.com/read/27802919/the-microbiome-of-neotropical-ticks-parasitizing-on-passerine-migratory-birds
#11
Khemraj Budachetri, Jaclyn Williams, Nabanita Mukherjee, Michael Sellers, Frank Moore, Shahid Karim
Seasonal migration of passerine birds between temperate North America and tropical Central and South America is an ecological phenomenon. Migration of birds has been associated with the introduction of ectoparasites like ticks or tick-borne pathogens across the avian migration routes. In this study, the microbial diversity was determined in the ticks and bird DNA samples using 454 pyrosequencing of bacterial 16S rRNA gene. Tick DNA samples showed the dominance of genera Lactococcus, Francisella, Raoultella, Wolbachia and Rickettsia across all the ticks, but birds DNA did not share common microbial diversity with ticks...
January 2017: Ticks and Tick-borne Diseases
https://www.readbyqxmd.com/read/27802578/open-and-compressed-conformations-of-francisella-tularensis-clpp
#12
Laura Díaz-Sáez, Genady Pankov, William N Hunter
Caseinolytic proteases are large oligomeric assemblies responsible for maintaining protein homeostasis in bacteria and in so doing influence a wide range of biological processes. The functional assembly involves three chaperones together with the oligomeric caseinolytic protease catalytic subunit P (ClpP). This protease represents a potential target for therapeutic intervention in pathogenic bacteria. Here, we detail an efficient protocol for production of recombinant ClpP from Francisella tularensis, and the structural characterization of three crystal forms which grow under similar conditions...
November 1, 2016: Proteins
https://www.readbyqxmd.com/read/27790972/introduction-and-persistence-of-tularemia-in-bulgaria
#13
Kerstin Myrtennäs, Krustyu Marinov, Anders Johansson, Marcin Niemcewicz, Edvin Karlsson, Mona Byström, Mats Forsman
INTRODUCTION: Outbreaks of the zoonotic disease tularemia occurred in north-east Bulgaria in the 1960s. Then came 30 years of epidemiological silence until new outbreaks occurred in west Bulgaria in the 1990s. To investigate how bacterial strains of Francisella tularensis causing tularemia in wildlife and humans in the 1960s and the 1990s were related, we explored their genetic diversity. MATERIAL AND METHODS: Ten F. tularensis genomes from the 1960s (n=3) and the 1990s (n=7) were sequenced, assigned to canonical single-nucleotide polymorphism (canSNP) clades, and compared to reference genomes...
2016: Infection Ecology & Epidemiology
https://www.readbyqxmd.com/read/27786577/regulation-of-lysosomal-dynamics-and-autophagy-by-ctsb-cathepsin-b
#14
Si Ming Man, Thirumala-Devi Kanneganti
Cysteine cathepsins are responsible for driving proteolytic degradation within the lysosome and in the extralysosomal milieu. They also have an integral role in autophagy, antigen presentation, cellular stress signaling, metabolism and lysosome-dependent cell death. Here, we discuss our findings on the role of CTSB (cathepsin B), a member of the cysteine cathepsin family, in regulating the bioavailability of lysosomes and autophagosomes and consider how this regulatory response influences host susceptibility to infectious agents...
October 27, 2016: Autophagy
https://www.readbyqxmd.com/read/27731377/identification-distribution-and-population-dynamics-of-francisella-like-endosymbiont-in-haemaphysalis-doenitzi-acari-ixodidae
#15
Jian-Nan Liu, Zhi-Jun Yu, Li-Meng Liu, Ning-Xin Li, Rong-Rong Wang, Chun-Mian Zhang, Jing-Ze Liu
Francisella-like endosymbionts (FLEs) with significant homology to Francisella tularensis (γ-proteobacteria) have been characterized in several tick species, whereas knowledge on their distribution and population dynamics in ticks remains meager. Hence, in the current study, we identified a novel Francisella-like endosymbiont (FLEs-Hd) from the tick Haemaphysalis doenitzi and evaluated the putative functions of this symbiont. Results indicated that FLEs-Hd had 100% infection rate and a perfect vertical transmission in H...
October 12, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27714591/mitogen-activated-protein-kinases-mapks-are-modulated-during-francisella-tularensis-infection-but-inhibition-of-extracellular-signal-regulated-kinases-erks-is-of-limited-therapeutic-benefit
#16
R J Saint, R V D'Elia, C Bryant, G C Clark, H S Atkins
Francisella tularensis is a Gram-negative intracellular bacterium that causes the disease tularemia. The disease can be fatal if left untreated and there is currently no licenced vaccine available; the identification of new therapeutic targets is therefore required. Toll-like receptors represent an interesting target for therapeutic modulation due to their essential role in generating immune responses. In this study, we analysed the in vitro expression of the key mitogen-activated protein kinases (MAPKs) p38, JNK and ERK in murine alveolar macrophages during infection with F...
December 2016: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/27695643/francisella-tularensis-immune-cell-activator-suppressor-or-stealthy-evader-the-evolving-view-from-the-petri-dish
#17
Kristen M Holland, Sarah J Rosa, Karsten R O Hazlett
One of the hallmarks of pulmonary tularemia, which results from inhalation of Francisella tularensis - a significant bioterrorism concern, is the lack of an acute TH1-biased inflammatory response in the early phase of disease (days 1-3) despite significant bacterial loads. In an effort to understand this apparent hypo-responsiveness, many laboratories have utilized in vitro cell-based models as tools to probe the nature and consequences of host cell interactions with F. tularensis. The first uses of this model suggested that mammalian host cells recognize this bacterium principally through TLR2 to evoke a robust, classical TH1-biased cytokine response including TNF, IL-6, IL-1β, and IFN-γ...
June 2016: Journal of Bioterrorism & Biodefense
https://www.readbyqxmd.com/read/27693356/irgb10-liberates-bacterial-ligands-for-sensing-by-the-aim2-and-caspase-11-nlrp3-inflammasomes
#18
Si Ming Man, Rajendra Karki, Miwa Sasai, David E Place, Sannula Kesavardhana, Jamshid Temirov, Sharon Frase, Qifan Zhu, R K Subbarao Malireddi, Teneema Kuriakose, Jennifer L Peters, Geoffrey Neale, Scott A Brown, Masahiro Yamamoto, Thirumala-Devi Kanneganti
The inflammasome is an intracellular signaling complex, which on recognition of pathogens and physiological aberration, drives activation of caspase-1, pyroptosis, and the release of the pro-inflammatory cytokines IL-1β and IL-18. Bacterial ligands must secure entry into the cytoplasm to activate inflammasomes; however, the mechanisms by which concealed ligands are liberated in the cytoplasm have remained unclear. Here, we showed that the interferon-inducible protein IRGB10 is essential for activation of the DNA-sensing AIM2 inflammasome by Francisella novicida and contributed to the activation of the LPS-sensing caspase-11 and NLRP3 inflammasome by Gram-negative bacteria...
October 6, 2016: Cell
https://www.readbyqxmd.com/read/27671061/a-bioluminescent-francisella-tularensis-schu-s4-strain-enables-noninvasive-tracking-of-bacterial-dissemination-and-the-evaluation-of-antibiotics-in-an-inhalational-mouse-model-of-tularemia
#19
Charlotte A Hall, Helen C Flick-Smith, Sarah V Harding, Helen S Atkins, Richard W Titball
Bioluminescence imaging (BLI) enables real-time, noninvasive tracking of infection in vivo and longitudinal infection studies. In this study, a bioluminescent Francisella tularensis strain, SCHU S4-lux, was used to develop an inhalational infection model in BALB/c mice. Mice were infected intranasally, and the progression of infection was monitored in real time using BLI. A bioluminescent signal was detectable from 3 days postinfection (3 dpi), initially in the spleen and then in the liver and lymph nodes, before finally becoming systemic...
December 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27670740/sensitivity-and-specificity-of-real-time-pcr-and-bacteriological-culture-for-francisellosis-in-farm-raised-nile-tilapia-oreochromis-niloticus-l
#20
G B N Assis, T F de Oliveira, I A Gardner, H C P Figueiredo, C A G Leal
Despite the worldwide occurrence of Francisella noatunensis subsp. orientalis (Fno) infection in farmed tilapia, sensitivity and specificity estimates of commonly used diagnostic tests have not been reported. This study aimed to estimate the sensitivity and specificity of bacteriological culture and qPCR to detect Fno infection. We tested 559 fish, sampled from four farms with different epidemiological scenarios: (i) healthy fish in a hatchery free of Fno; (ii) targeted sampling of diseased fish with suggestive external clinical signs of francisellosis during an outbreak; (iii) convenience sampling of diseased and clinically healthy fish during an outbreak; and (iv) sampling of healthy fish in a cage farm without a history of outbreaks, but with francisellosis reported in other farms in the same reservoir...
September 27, 2016: Journal of Fish Diseases
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